The Osteoclast is a multinucleated cell that actively resorbs bone. This bone resorptive process is an essential step in the sequential process of bone remodeling as well as in some disease processes. Stimulation of the osteoclast to resorb bone and inhibit the osteoblast from making bone probably involves the expression of an array of genes. The purpose of these studies is to attempt to elucidate the mechanism of bone resorption-related genes with emphasis on the characterization of these genes using the human osteoclastoma tumor system. Novel resorptive-related gene clones were obtained from an osteoclastoma cDNA library by differential screening using probes from the giant cell tumor and cultured stromal cells form the same tumor. In situ hybridization will be used to screen these genes for cell type specifity. Full length cDNA sequences will be respectively used for protein production and studies of regulation of resorption-related genes, in particular genes involved in osteoblast-osteoclast signaling. This approach has a high probability of uncovering osteoblast and osteoclast function related to the resorption process. Key Words: osteclast, osteclastoma, resorption related